Summary
S-adenosyl-l-methionine (AdoMet) is synthesized by transfer of the adenosyl moiety of ATP to the sulfur atom of methionine. This reaction is catalysed by AdoMet synthetase. In all eukaryotic organisms studied so far, multiple forms of AdoMet synthetases have been reported and from their recent study, it appears that AdoMet synthetase is an exceptionally well conserved enzyme through evolution. In Saccharomyces cerevisiae, we have demonstrated the existence of two AdoMet synthetases encoded by genes SAM1 and SAM2. Yeast, which is able to concentrate exogenously added AdoMet, is thus a particularly useful biological system to understand the role and the physiological significance of the preservation of two almost identical AdoMet synthetases. The analysis of the expression of the two SAM genes in different genetic backgrounds during growth under different conditions shows that the expression of SAM1 and SAM2 is regulated differently. The regulation of SAM1 expression is identical to that of other genes implicated in AdoMet metabolism, where as SAM2 shows a specific pattern of regulation. A careful analysis of the expression of the two genes and of the variations in the methionine and AdoMet intracellular pools during the growth of different strains lead us to postulate the existence of two different AdoMet pools, each one suppplied by a different AdoMet synthetase but in equilibrium with each other. This could be a means of storing AdoMet whenever this metabolite is overproduced, thus avoiding the degradation of a metabolite the synthesis of which is energetically expensive.
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References
Alix J-H (1982) Molecular aspects of the in vivo and in vitro effects of ethionine, an analog of methionine. Microbiol Rev 46:281–295
Cabrero C, Alemany S (1988) Conversion of rat liver S-adenosyl-l-methionine synthetase from high-Mr form to low-Mr form by LiBr. Biochim Biophys Acta 952:277–281
Cantoni GL (1953) S-Adenosylmethionine: a new intermediate formed enzymatically from L-methionine and ATP. J Biol Chem 204:403–416
Cherest H, Surdin-Kerjan Y, Antoniewski J, de Robichon-Szulmajster H (1973) Effects of regulatory mutations upon methionine biosynthesis in Saccharomyces cerevisiae: loci eth2, eth3, eth10. J Bacteriol 115:1084–1093
Cherest H, Surdin-Kerjan Y, Exinger F, Lacroute F (1978) S-adenosylmethionine requiring mutants in Saccaromyces cerevisiae: evidence for the existence of two methionine adenosyl transferases. Mol Gen Genet 163:153–167
Cohen SN, Chang ACY, Hsu L (1972) Non-chromosomal antibiotic resistance in bacterial genetic transformation of E. coli by R factor DNA. Proc Natl Acad Sci USA 69:2110–2114
Farooqui JZ, Woo Lee H, Kim S, Park WK (1983) Studies on compartmentation of S-adenosyl-l-methionine in Saccharomyces cerevisiae and isolated rat hepatocytes. Biochim Biophys Acta 747:342–351
Ferro AJ, Spence KD (1973) Induction and repression in the Sadenosylmethionine and methionine biosynthetic systems of Saccharomyces cerevisiae. J Bacteriol 116:812–817
Hodgson CP, Fisk RZ (1987) Hybridization probe size control: optimized “oligolabelling”. Nucleic Acids Res 15:6295
Hoffman CS, Winston F (1987) A ten-minute DNA preparation from yeast efficiently releases autnomous plasmids for transformation of Escherichia coli. Gene 57:267–272
Horikawa S, Ishikawa M, Ozasa H, Tsukuda K (1989) Isolation of a cDNA encoding the rat liver S-adenosylmethionine synthetase. Eur J Biochem 184:497–501
Horikawa S, Sasuga J, Shimizu K, Ozasa H, Tsukada K (1990) Molecular cloning and nucleotide sequence of cDNA encoding the rat kidney S-adenosylmethionine synthetase. J Biol Chem 265:13683–13686
Ish-Horowicz D, Burke JF (1981) Rapid and efficient cosmid cloning. Nucleic Acids Res 9:2989–2998
Ito H, Fukuda K, Murata K, Kimura A (1983) Transformation of intact yeast cells treated with alkali cations. J Bacteriol 153:163–168
Kerjan P, Cherest H, Surdin-Kerjan Y (1986) Nucleotide sequence of the Saccharomyces cerevisiae MET25 gene. Nucleic Acids Res 14:7861–7871
Kredich NH, Tomkins GM (1966) The enzymatic synthesis of Lcysteine in Escherichia coli and Salmonella typhimurium. J Biol Chem 241:4955–4965
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Markham JD, DeParisis J, Gatmaitan J (1984) The sequence of MetK, the structural gene for S-adenosylmethionine synthetase in Escherichia coli. J Biol Chem 259:14505–14507
Miller JH (1972) Experiments in molecular genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York
Mudd SJ, Levy HL (1983) Disorders of transsulfuration. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw Hill Book Company, New York, pp 522–559
Peleman J, Boerjan W, Engler G, Seurink J, Botterman J, Alliote T, Van Montagu M, Inzé D (1989a) Strong cellular preference in the expression of a housekeeping gene of Arabidopsis thaliana encoding S-adenosylmethionine synthetase. Plant Cell 1:81–93
Peleman J, Saito K, Cottyn B, Engler G, Seurink J, Van Montagu M, Inzé D (1989b) Structure and expression analyses of the S-adenosylmethionine synthetase gene family in Arabidopsis thaliana. Gene 84:359–369
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York
Satishchandran C, Taylor JC, Markham GD (1990) Novel Escherichia coli K-12 mutants impaird in S-adenosylmethionine synthesis. J Bacteriol 172:4489–4496
Shapiro SK, Ehninger DJ (1966) Methods for the analysis and preparation of Adenosylmethionine and Adenosylhomocysteine. Anal Biochem 15:323–333
Sherman F, Fink GR, Hicks JB (1979) Methods in yeast genetics: A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York
Surdin-Kerjan Y, de Robichon-Szulmajster H (1975) Existence of two levels of repression in the biosynthesis of methionine in Saccharomyces cerevisiae: effect of lomogungin on enzyme synthesis. J Bacteriol 122:367–374
Tabor CW, Tabor H (1985) Polyamines in microorganisms. Microbiol Rev 49:81–99
Thomas D, Surdin-Kerjan Y (1987) SAM1, the structural gene for one of the S-adenosylmethionine synthetases in Saccharomyces cerevisiae. J Biol Chem 262:16704–16709
Thomas D, Rothstein R, Rosenberg N, Surdin-Kerjan Y (1988) Sam2 encodes the second methionine S-adenosyl transferase in Saccharomyces cerevisiae: physiology and regulation of both enzymes. Mol Cell Biol 8:5132–5139
Thomas D, Cherest H, Surdin-Kerjan Y (1989) Elements involved in S-adenosylmethionine mediated regulation of the Saccharomyces cerevisiae MET25 gene. Mol Cell Biol 9:3292–3298
Wiebers JL, Garner MR (1967) Acyl derivatives of homoserine as substrate for homocysteine synthesis in Neurospora crassa, yeast and Escherichia coli. J Biol Chem 242:5644–5649
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Communicated by W. Gajewski
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Thomas, D., Surdin-Kerjan, Y. The synthesis of the two S-adenosyl-methionine synthetases is differently regulated in Saccharomyces cerevisiae . Mol Gen Genet 226, 224–232 (1991). https://doi.org/10.1007/BF00273607
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DOI: https://doi.org/10.1007/BF00273607